Allopurinol Tablets
»Allopurinol Tablets contain not less than 93.0percent and not more than 107.0percent of the labeled amount of allopurinol (C5H4N4O).
Packaging and storage— Preserve in well-closed containers.
Identification— Extract a quantity of finely powdered Tablets,equivalent to about 50mg of allopurinol,by trituration with 10mLof 0.1Nsodium hydroxide.Filter,acidify the filtrate with 1Nacetic acid,collect the precipitated allopurinol (allow 10to 15minutes for sufficient precipitation to occur),wash the precipitate with 3mLof dehydrated alcohol,in portions,and finally wash with 4mLof anhydrous ethyl ether.Allow to dry in air for 15minutes,then dry at 105for 3hours:the residue so obtained meets the requirements for the Identificationtest under Allopurinol.
Dissolution á711ñ—
Medium: 0.01Nhydrochloric acid;900mL.
Apparatus 2: 75rpm.
Time: 45minutes.
Standard stock solution— Prepare a stock solution by transferring about 40mg of USP Allopurinol RS,accurately weighed,to a 200-mLvolumetric flask.Add 10mLof 0.1Nsodium hydroxide,sonicate for about 2minutes,shake by mechanical means for about 10minutes,dilute with Dissolution Medium to volume,and mix.
Standard solution— Dilute the Standard stock solutionwith Dissolution Medium to obtain a solution having a concentration similar to that expected in the solution under test.
Procedure— Determine the amount of C5H4N4Odissolved by employing UVabsorption at the wavelength of maximum absorbance at about 250nm on filtered portions of the solution under test,suitably diluted with Dissolution Medium,in comparison with the Standard solution.
Tolerances— Not less than 75%(Q)of the labeled amount of C5H4N4Ois dissolved in 45minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Assay— [NOTE—Do not allow the Mobile phase to remain in the column overnight.After performing the procedure,flush the system with water for not less than 20minutes,and then flush with methanol for 20minutes.]
Mobile phase— Prepare a filtered and degassed 0.05Msolution of monobasic ammonium phosphate.
Internal standard solution— On the day of use,dissolve about 50mg of hypoxanthine in 10mLof 0.1Nsodium hydroxide,shake by mechanical means until dissolved (about 10minutes),dilute with water to 50mL,and mix.
Standard preparation— On the day of use,transfer about 50mg of USP Allopurinol RS,accurately weighed,to a 50-mLvolumetric flask,add 10mLof 0.1Nsodium hydroxide,shake by mechanical means for 10minutes,dilute with water to volume,and mix.Transfer 4.0mLof this solution and 2.0mLof Internal standard solutionto a 200-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 50mg of allopurinol,to a 50-mLvolumetric flask,add 10mLof 0.1Nsodium hydroxide,shake by mechanical means for 10minutes,add water to volume,and mix.[NOTE—From this point,conduct the remainder of the Assay without delay.]Filter,rejecting the first 10mLof the filtrate.Transfer 4.0mLof the filtrate and 2.0mLof Internal standard solutionto a 200-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 254-nm detector and a 4-mm ×30-cm column that contains packing L1.The flow rate is about 1.5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative retention times are about 0.6for hypoxanthine and 1.0for allopurinol;the resolution,R,between the analyte and internal standard is not less than 5;and the relative standard deviation for replicate injections is not more than 3.0%.
Procedure— Separately inject equal volumes (about 15µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of allopurinol (C5H4N4O)in the portion of Tablets taken by the formula:
2.5C(RU/RS),
in which Cis the concentration,in µg per mL,of USP Allopurinol RSin the Standard preparation;and RUand RSare the peak response ratios of allopurinol to hypoxanthine obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(PA4)Pharmaceutical Analysis 4
USP28–NF23Page 68
Pharmacopeial Forum:Volume No.29(3)Page 604
Phone Number:1-301-816-8251